The long-term objectives of this research are to develop practical methods for preparation of stereopure antisense phosphorothioates as potentially improved anticancer and antiviral agents to replace, if warranted, the current stereorandom antisense phosphorothioates under investigation by Lynx and other antisense drug discovery companies. The particular disease targets for Lynx include chronic myelogenous leukemia, malignant melanoma, glioblastoma, 3-cell lymphoma, Kaposi's sarcoma, and infection by human immunodeficiency virus, type 1 (HIV-1), as well as hepatitis B and C virus (HBV and HCV) and restenosis. Optimization of automated solid-phase synthesis by the recently explored oxathiaphospholane method will be studied in parallel with optimally shortened project compounds using cell culture assays available in-house and through various existing collaborations. The rate of synthetic progress will determine whether in vivo efficacy studies will be carried out collaboratively during Phase II or thereafter. Antisense drug discovery is now being pursued by many new as well as established drug companies. Stereorandom phosphorothioate oligomers are the leading antisense drugs under development. Possible advantages of stereopure phosphorothioates could expand the commercial success of this new technology, which is related to issued broad-claim U.S. government patents licensed by Lynx and two other companies.